Naslov
Radiation sterilization of ketoprofen

Autori
Katušin-Ražem, Branka ; Hamitouche, Katia ; Maltar-Strmečki, Nadica ; Kos, Karmen ; Pucić, Irina ; Britvić-Budičin, Smiljana ; Ražem, Dušan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2003 International Meeting on Radiation Processing - Conference Program and Abstracts / - Chicago (IL) : STERIS Isomedix Services, 2003, 291-291

Skup
2003 IMRP -Advancing Ionization Technology

Mjesto i datum
Chicago (IL), Sjedinjene Američke Države, 07.09.2003. - 12.09.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ketoprofen; radiation sterilization; radiation degradation; DSC; ESR; HPLC; IR; UV; XRD; Ames test

Sažetak
Irradiation is an attractive technique for sterilization of pharmaceutical substances which are otherwise sensitive to traditional methods of sterilization because it does not involve heating, does not leave residuals, and can be carried out in the final packaging. Consequently, sterility assurance level higher than 0.999, 999 could be expected at 25 kGy in products made according to good manufacturing practice. Profens are potent nonsteroidal anti-inflammatory drugs. Sterile profens are required in the preparation of intramuscular and/or subcutaneous injections and eye drops. Ketoprofen [2-(3-benzoylphenyl)propionic acid] is widely used and is one of the most popular profens. The feasibility of radiation sterilization of ketoprofen in dry powder form was investigated. While sterilization of dry powder does not present the advantage of treatment in the final packaging, and would require sterile packaging conditions for the preparation of sterile injection solutions, much smaller radiation-induced degradation could be expected in that form. Samples of solid ketoprofen irradiated with 25 kGy sterilization dose were characterized by physico-chemical methods, both those specified by the European Pharmacopeia, as well as by some additional ones. High performance liquid chromatography (HPLC), ultraviolet spectrophotometry (UV), infrared spectrophotometry (IR), differential scanning calorimetry (DSC), X-ray diffraction patterns (XRD), and electron spin resonance (ESR) spectroscopy were applied. Physico - chemical tests do not show any significant degradation at sterilization dose of 25 kGy. To determine the nature, extent and direction of possible radiation-induced changes in irradiated ketoprofen, the substance was irradiated to extremely high doses, up to 4000 kGy. Ketoprofen has proven to be very resistant to irradiation. XRD pattern did not show any difference between unirradiated and samples irradiated with 2000 kGy. With DSC and IR spectrophotometry it was possible to detect changes only in ketoprofen irradiated with 2000 kGy and higher. HPLC analyses of samples irradiated with 3000 kGy have shown about 5% destruction of ketoprofen. While some radiation chemical products, such as acetyl benzophenon, are not unique and are originally present in the parent compound as an impurity generated during production and handling, irradiation generates a few specific radiolytic products. However, genotoxicity study using Ames test have shown no undue mutagenicity of unirradiated, as well as of ketoprofen irradiated with 3000 kGy. Moreover, the oily mixure of impurities and lipophylic radiolytic products, which were isolated by hexane extraction of alkalic water solution of ketoprofen irradiated with 3000 kGy were found to be non-mutagenic by the Ames test. In conclusion, radiation is a convenient method for sterilization of solid ketoprofen.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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